Local excision and postoperative radiotherapy for distal rectal cancer

PII S0360-3016(01)01545-0

CLINICAL INVESTIGATION Rectum

LOCAL EXCISION AND POSTOPERATIVE RADIOTHERAPY FOR DISTALRECTAL CANCER

RICHARD BENSON, M.B.,* C. SHUN WONG, M.D.,† BERNARD J. CUMMINGS, M.B.,†

JAMES BRIERLEY, M.B.,† PAMELA CATTON, M.D.,† JOLIE RINGASH, M.D.,† AND

MOHAMED ABDOLELL, M.SC.‡

*Department of Oncology, Addenbrooke’s Hospital, Cambridge, United Kingdom; Departments of†Radiation Oncology and‡Biostatistics, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada

Purpose: To assess the outcome following local excision and postoperative radiotherapy (RT) for distal rectalcarcinoma.Materials and Methods: Seventy-three patients received postoperative radiotherapy following local surgery forprimary rectal carcinoma at Princess Margaret Hospital from 1983 to 1998. Selection factors for postoperativeRT were patient preference, poor operative risks, and “elective” where conservative therapy was regarded asoptimal therapy. Median distance of the primary lesion from the anal verge was 4 cm (range, 1–8 cm). Therewere 24 T1, 36 T2, and 8 T3 lesions. The T category could not be determined in 5. Of 55 tumor specimens in whichmargins could be adequately assessed, they were positive in 18. RT was delivered using multiple fields by 6- to25-MV photons. Median tumor dose was 50 Gy (range, 38–60 Gy), and 62 patients received 50 Gy in 2.5-Gy dailyfractions. The tumor volume included the primary with 3–5 cm margins. No patients received adjuvantchemotherapy. Median follow-up was 48 months (range, 10–165 months).Results: Overall 5-year survival and disease-free survival were 67% and 55%, respectively. Tumor recurrencewas observed in 23 patients. There were 14 isolated local relapses; 6 patients developed local and distant disease;and 3 relapsed distantly only. For patients with T1, T2, and T3 lesions, 5-year local relapse-free rates were 61%,75%, and 78%, respectively, and 5-year survival rates were 76%, 58%, and 33%, respectively. The 5-year localrelapse-free rate was lower in the presence of lymphovascular invasion (LVI) compared to no LVI, 52% vs. 89%,p 5 0.03, or where tumor fragmentation occurred during local excision compared to no fragmentation, 51% vs.76%, p 5 0.02. Eleven of 14 patients with local relapse only underwent abdominoperineal resection, 8 achievedlocal control, and 4 remained cancer free. The ultimate local control, including salvage surgery, was 86% at 5 and10 years. The 5-year colostomy-free rate was 82%. There were 2 patients who experienced RTOG Grade 3 latecomplications, and 1 with Grade 4 complication (bowel obstruction requiring surgery).Conclusion: The local relapse rate for patients with T1 disease was high compared to other series of local excisionand postoperative RT. Patients with LVI or tumor fragmentation during excision have high local relapse ratesand may not be good candidates for conservative surgery and postoperative RT. © 2001 Elsevier Science Inc.

Rectal carcinoma, Local excision, Radiotherapy.

INTRODUCTION

Since Miles’s (1) original study, the standard, radical treat-ment for low rectal cancer has been an abdominoperinealresection (APR) with removal of the regional lymph nodes.This requires the patient to have a permanent colostomy,and there are significant risks of complications includingdeath (2). For some low rectal tumors, radical excision witha coloanal anastamosis may be possible. This sphincter-saving approach is a complex procedure associated with anincreased complication rate (3).

In selected patients with favorable tumors that are 3 cmor less in maximum diameter, well or moderately differ-entiated, mobile, exophytic, and with no transmural in-

vasion, local therapy can achieve high rates of cure.Local therapy allows preservation of sphincter functionand reduces the operative morbidity and mortality com-pared to a radical procedure. Approaches to local treat-ment include contact X-ray therapy, transanal excision,electrocoagulation and fulguration, and trans-sphinctericand trans-sacral excision (4 – 6). For lesions that areconsidered unfavorable with a high risk of local recur-rence and of nodal disease, pelvic radiotherapy (RT),with or without chemotherapy, has been recommendedfollowing local excision to maximize local control whilepreserving sphincter function (7). Unfavorable lesionsare generally lesions with invasion into muscularis pro-

Reprint requests to: Dr. C. S. Wong, Department of RadiationOncology, Princess Margaret Hospital, 610 University Avenue,Toronto, Ontario, Canada. E-mail: [email protected]

Presented at the American Society for Therapeutic Radiologyand Oncology (ASTRO) 42nd Annual Meeting, Boston, MA.

Accepted for publication 23 February 2001.

Int. J. Radiation Oncology Biol. Phys., Vol. 50, No. 5, pp. 1309–1316, 2001Copyright © 2001 Elsevier Science Inc.Printed in the USA. All rights reserved

0360-3016/01/$–see front matter

1309

pria, poor differentiation, lymphatic or blood vessel in-vasion, and positive margins.

Here we report our experience with postoperative RTafter local excision in the management of early-stage rectalcarcinoma with unfavorable features.

METHODS AND MATERIALS

SelectionAll patients referred to Princess Margaret Hospital

(PMH) between 1983 and 1998 following local excision ofrectal cancer were identified. Patients treated with localexcision alone, with metastatic disease at diagnosis, or whowere referred back to the surgeon for a radical operation,were not included in this study. The study period wasselected to coincide with the introduction of a policy toirradiate the rectum with a margin only rather than thewhole pelvis.

Eighty patients were identified with carcinoma of therectum treated by local excision and RT. Seven patientswere excluded because RT was given for locally recurrentrectal cancer (n 5 4), for carcinomain situ (n 5 1),preoperatively (n 5 1), or with palliative intent (n 5 1).Induration at the site of excision was not an exclusionfactor, because this was usually considered a post-surgicalphenomenon. Nine patients were included in a previousreport of 25 patients (8).

The decision to offer postoperative RT was based on anumber of factors. including pathologic features of thetumor, patient preference, and the patient’s general medicalcondition. From 1993, selection criteria for treatment withlocal excision and radiotherapy at PMH were based on aprevious study (8). Exclusion criteria included well- ormoderately differentiated T1 lesions that were under 3 cm(treated with excision alone), and T3 lesions (APR recom-mended), unless the patients were considered unfit for orrefused radical surgery. Since 1993, a single T1 lesion and8 T3 lesions were treated outside the exclusion criteriabecause of patient preference or medical condition preclud-ing radical surgery.

Demographics (Table 1)Forty-one patients were male and 32 were female. The

median age at diagnosis was 65 (range, 40–88). In terms ofselection factors for postoperative RT, 35 patients refused apermanent colostomy. Ten were considered medically unfitfor radical surgery, and 28 were recommended local exci-sion followed by RT as optimal therapy after accounting fora combination of factors, including comorbid medical con-ditions, patient preference, and perceived risk of local re-currence.

SymptomsThe main presenting symptoms were rectal bleeding

(78%), change in bowel habit (30%), change in stool con-sistency (11%), and sensation of a rectal mass (10%). Twocancers were diagnosed at a routine medical examination.

Symptoms had been present for 1–38 months (median, 5.5months) before diagnosis.

SurgeryGenerally, local excision was performed at the surgeon’s

discretion, and patients were then referred to PMH for aradiotherapy opinion. Surgical techniques included poste-rior sacrectomy (3), transanal local excision (49), and elec-trocoagulation or fulguration (21). All tumors were mobile,49 were polypoid, 20 were sessile, and 5 were ulceroinva-sive. Median distal distance of the lesion from anal vergewas 4 cm (1–8 cm).

PathologyThe pathology was reviewed by gastrointestinal onco-

logic reference pathologists in 52 cases (71%). All lesionswere adenocarcinomas, with grade classified as well differ-entiated (WD) in 4, moderately differentiated (MD) in 60,poorly differentiated (PD) in 4, and unspecified in 5. Tumor(T) category according to the TNM classification of theUICC 1996 was T1 in 24 patients, T2 in 36, T3 in 8, and Txin 5. The size ranged from 0.3 to 7 cm (median, 3 cm).

Table 1. Characteristics of patients who underwent localexcision and postoperative radiotherapy for rectal cancer

Characteristic n (%)

GenderMale 41 (56)Female 32 (44)

Age (in years)# 65 37 (50). 65 36 (50)

Surgical ProcedureTransanal excision 49 (67)Trans-sacral excision 3 (4)Electrocoagulation 21 (29)

T stageT1 24 (33)T2 36 (49)T3 8 (11)Tx 5 (7)

GradeWell differentiated 4 (6)Moderately differentiated 60 (82)Poorly differentiated 4 (6)Not stated 5 (7)

MarginsPositive 18 (25)Negative 37 (50)Unknown 18 (25)

Size# 3 cm 46 (63). 3 cm 27 (37)

Lymphovascular invasionPositive 12 (16)Negative 21 (29)Unknown 40 (55)

Fragmented specimenYes 20 (27)No 53 (73)

1310 I. J. Radiation Oncology● Biology ● Physics Volume 50, Number 5, 2001

Pathologic margin status was negative in 37, positive in 18,and was stated uncertain or not specified in the pathologyreport in 18. Twenty specimens were fragmented, and theremainder were excised in one piece. Lymphatic or vascularinvasion (LVI) was detected in 12 cases, negative in 21, andunknown or not reported in 40. Three specimens had 1–3nodes detected that were negative. A single patient hadnode-positive disease.

StagingStaging was by clinical examination. Liver ultrasound,

radionuclide scan, or CT—abdomen/pelvis scan was per-formed in 63% of patients. CEA was performed in 46patients and was within the normal range in all cases.Transrectal ultrasound was performed preoperatively on 14.

RadiotherapyMedian tumor dose was 50 Gy (range, 38.25–60 Gy), and

62 patients received 50 Gy in 20 daily fractions at 2.5 Gyper fraction. The tumor dose in all patients was$ 45 Gywith the exception of 1 who died during treatment of unre-lated causes (38.25 Gy). Treatment interruption of 5 days orlonger (5–14 days) occurred in 5 patients due to publicholidays (2), toxicity (2), and following a road traffic acci-dent (1). Seventy-two patients received the prescribed doseof radiotherapy; 1 patient did not complete the course oftreatment. Overall treatment time was 20–53 days, with amedian of 29 days.

The target volume encompassed the primary tumor andperi-rectal lymph nodes with a 3–5 cm margin. Treatmentwas delivered with high-energy photons (6, 18, or 25 MV)using 3- (n 5 20) or 4-field (n 5 53) techniques in a singlephase (n 5 62) or 2 (n 5 11) phases. For single-phasetechnique, the median volume was of 1728 cm3 (720–3120cm3), corresponding to a field size of 123 123 12 cm. For2-phase treatments, the volume ranged from 2184 to 3328cm3 in Phase 1 (median of 2835 cm3 or 143 13.53 15 cm)and 990–2352 cm3 in Phase 2 (median, 1320 cm3 or 11 311 3 11 cm).

None of the patients received concurrent or adjuvantchemotherapy.

Follow-upPatients were followed up every 3–6 months for 5 years

after completing RT, and, in addition, were also seen reg-ularly by their surgeons. Evaluation consisted of a physicalexamination including a rectal examination at each visit.Liver ultrasound or CT and CEA were not performed as partof routine follow-up. Local recurrence was defined as dis-ease at the site of resection or in the perirectal lymphaticswithin the treatment volume. Distant metastases were de-fined as recurrences outside the pelvis. All local recurrenceswere recorded as a local failure even if distant failure wasthe first event. Radiotherapy complications were scoredretrospectively according to the RTOG–EORTC scoringsystem for acute and late complications. Median follow-upwas 48 months (10–165 months). Two patients were lost to

follow-up at 15 and 34 months; the remaining patients werefollowed for at least 5 years.

StatisticsSurvival endpoints were calculated using time to event

from the date of surgery. Kaplan–Meier (9) survival curveswere used to estimate overall survival and for univariateanalyses of survival data. Parameters analyzed includedpatient age, gender, tumor size, tumor grade, T category,margin status, specimen fragmentation, lymphovascular in-vasion, and interval to radiotherapy. In the case of univar-iate analyses with multilevel categorical variables, the log–rank test (10) was used to compare the survival profilesbetween groups. Cox proportional hazards (11) modelingwas employed where more than one covariate was consid-ered simultaneously as a risk factor for survival outcome.The proportional hazards assumption was tested, and noevidence was found to indicate that the assumption wasviolated. Descriptive statistics were also presented to definethe sample. SAS (12) was used for the statistical analyses,and Splus (13) was used to generate the Kaplan–Meiersurvival plots.

RESULTS

ComplicationsFollowing local surgery, hemorrhage and fistula occurred

in 1 case after a posterior sacral approach. This resolvedwith conservative management. Self-limited rectal inconti-nence occurred in 2 patients and rectal bleeding in 1. All ofthese complications resolved spontaneously.

Early RT complications were mainly RTOG Grade 1 and2, and all resolved shortly after completing RT. Two pa-tients experienced RTOG Grade 3 diarrhea, necessitating abreak in treatment of 2 weeks, and, in 1 of these cases, i.v.fluid administration was required. Late RTOG Grade 1 and2 complications of radiotherapy included minor inconti-nence (n 5 3) and rectal bleeding (n 5 2). RTOG Grade 3complications included rectal stricture (n 5 1), bowel ob-struction (n 5 1), and impotence (n 5 1). A single patienthad an episode of small bowel obstruction requiring surgery(Grade 4).

Patterns of recurrenceRecurrences were seen in a total of 23 patients, 14 with

local recurrence alone, 6 with local recurrence and withdistant disease, and 3 with metastatic disease alone. Alllocal recurrences were at the site of the primary. Time torecurrence ranged from 4 to 53 months (median, 14 months)from date of surgery. Of the 6 with local and metastaticrecurrence, 3 had died from metastatic disease and 2 re-mained alive with metastatic disease. Of the group recurringwith metastatic disease alone, 2 of 3 had died, and 1 wasalive with metastases. No isolated regional recurrence wasobserved.

1311Local excision and postoperative radiotherapy for rectal cancer● R. BENSON et al.

Survival and local control ratesOverall survival was 67% and 41% at 5 and 10 years,

respectively (Fig. 1a). The log–rank test revealed no signif-icant influence of age, gender, time interval to radiotherapy,T category, margin status (positive vs. negative), grade(well and moderately vs. poorly differentiated), size (# 3cm vs. . 3 cm), and lymphovascular invasion (LVI)(present vs. absent) on survival (Table 2). There was asignificant difference in survival between patients with frag-mented and unfragmented specimens (p 5 0.04), Fig. 1b.

Disease-free survival (DFS) was 55% and 46% at 5 and10 years, respectively. Using log–rank test, the only param-eter that influenced DFS was fragmentation of the specimen(p 5 0.003), Table 2.

The local recurrence-free rate was 68% at both 5 and 10years (Fig. 2a). The log–rank test revealed a significant in-crease in local relapse where tumor fragmentation occurredduring local excision compared to no fragmentation,p 5 0.02,Fig. 2b, or, in the presence of LVI compared to no LVI,p 50.03, Fig. 2c. In multivariate analysis, only LVI proved to be asignificant predictor of local recurrence.

The 5- and 10-year event-free survival, when death fromany cause, local or distant recurrence, and RTOG late Grade 3or 4 complications were analyzed together, were 55% and44%, respectively. The actuarial colostomy-free rates at 5 and10 years were identical at 82%. Two patients who died at thetime of salvage APR were counted as having a colostomy.

Salvage surgeryFor the 14 isolated local recurrences, 11 were treated for

cure with an APR. In the group in whom a radical resection

was performed, 2 died from complications of their salvagesurgery (hemorrhage and heart failure). In both cases, thechoice of initial management by local excision and radio-therapy had been recommended because of anticipated risksof complications from radical resection and general anes-thetic. Three of 11 patients who underwent salvage surgeryfor local recurrence subsequently developed metastatic dis-ease, 1 developed both metastatic disease and further locallyrecurrent disease, and 1 died of local recurrence alone.

Four patients remained disease free at 3, 34, 48, and 68months from salvage surgery. Three of these patients werealive with no evidence of recurrence, and 1 patient died ofa second primary malignancy. Where recurrence was localand metastatic (n 5 6), 2 underwent APR and were locallycontrolled until death or last follow-up at 26 and 14 monthsfrom recurrence. The actuarial rate of local control includ-ing salvage was 86% at 5 and 10 years.

DISCUSSION

Early-stage disease (T1, T2, and N0) accounts for one-third of clinical presentations of rectal cancer. The NationalCancer Data Base Report on Patterns of Care for Adeno-carcinoma of the Rectum 1985–1995 (14) demonstrated atrend to increased use of local excision for treatment ofrectal cancer in the United States, with local excision ac-counting for up to 33% of treatment for Stage I tumors.

A review of the results of local excision as sole treatmentfor early-stage rectal carcinoma reported an overall rate oflocal recurrence of 24% (12–27%) (5). By stage, the local

Fig. 1. Overall actuarial survival probability (left), and the influence of specimen fragmentation on overall survival(right).


recurrence rates were: T1, 5%; T2, 18%; and T3, 22%. Mostseries of local excision alone exclude lesions unless they areT1 or T2,, 3 cm in maximum diameter, well or moderatelydifferentiated, margin negative, no evidence of LVI, and

have no ulceration or mucin production (4, 5, 15). Patientswho are treated with local excision and radiotherapy gen-erally have poorer prognostic features compared to those inseries of local excision alone. The 67% 5-year overall

Table 2. Effects of clinical and pathologic factors on overall survival (OS), disease-free survival (DFS), and local relapse-freerate (LRFR)

Characteristic

5-year actuarial results

n OS p DFS p LRFR p

GenderMale 41 57% 52% 67%Female 32 78% 59% 70%

Age (in years)# 65 37 60% 57% 73%. 65 36 74% 53% 66%

T stageT1 24 76% 59% 61%T2 36 58% 58% 79%T3 8 33% 38% 75%

Size# 3 cm 46 70% 60% 68%. 3 cm 27 62% 56% 68%

GradeWD 4 75% 50% 75%MD 60 67% 58% 73%PD 4 75% 75% 75%

MarginsNegative 37 74% 64% 77%Positive 18 65% 55% 70%

FragmentsUnfragmented 53 76% 66% 76%Fragmented 20 45% 0.04 26% 0.003 51% 0.02

Lymphovascular invasionAbsent 21 76% 69% 89%Present 12 45% 26% 52% 0.03

p by log–rank test (only given ifp , 0.05).

Fig. 2. Actuarial local relapse-free rate (left), and the influence of tumor fragmentation (middle) and lymphovascularinvasion (LVI) on local relapse-free rate (right).


survival after local excision and radiotherapy reported hereis comparable with other series that reported actuarial over-all survival rates of 70–80% at 5 years (16–20). The LRFRof 68% reported here was again similar to 5-year localcontrol rates of 73–90% reported in the literature (18, 20,21). In the series from Chakravartiet al. (21), the localcontrol rate after adjuvant radiotherapy fell from 90% at 5years to 57% at 8 years as a consequence of late failures.Better results have been reported, but these series generallyincluded patients with better prognosis disease (Tis and T1nonirradiated lesions) (22, 23). A 5-year local control rate ashigh as 96% has been reported for T1 and T2 lesions afterchemoradiotherapy (21).

Direct comparison of results of local excision to radicalsurgery is problematic, because most radical surgical serieshave reported results according to either the Dukes or themodified Astler–Coller staging systems, and both are de-pendent on nodal status. After local excision, the nodalstatus is unknown, and one might expect understaging. Theonly direct comparison of local excision and radiotherapyused retrospectively matched patients with Stage T1–2 N0M0 disease treated by local excision and radiotherapy orAPR (24). Local control and disease-free survival rates weresimilar except in the subset of patients with unfavorablepathology (poorly differentiated, lymphovascular invasion)who did worse after local therapy. Local recurrence ratesafter low anterior resection or APR without adjuvant treat-ment have varied from 0% to 27% for Dukes A (T1N0 andT2N0), and from 12% to 83% for Dukes B (T3/T4N0)disease (25, 26). Local recurrence rates after radical surgeryhave been reduced significantly with postoperative radio-therapy (27), chemoradiotherapy (28–30), and preoperativeradiotherapy (25, 26, 31–33).

Perhaps the best comparison of local excision and radio-therapy for rectal carcinoma with radical surgical series isthe ultimate local control rate, including patients success-fully salvaged after local failure. The 87% 5-year actuariallocal control rate reported here is very similar to the 90%rates reported by other series (17, 18). The 5-year colosto-my-free rate of 81% reported here is also comparable tothose in other series (17, 20).

In the present series, recurrences presented at up to 53months (median, 14 months) from diagnosis. Others havereported recurrences at up to 91 months, with a median timeto recurrence of 55 months (21). The median time to recur-rence appears to be increased by radiotherapy (21). There-fore, regular long-term follow-up should be continued, be-cause local recurrences may be salvageable. In our series,salvage surgery was performed in 11 of 14 local recur-rences, and 7 of these patients remained local disease free atdeath or last follow-up. Reports of successful salvage ofisolated local failures of approximately 50% have beendescribed (8, 16–18, 20, 21, 34, 35). Follow-up of thesepatients is mainly by clinical examination, because thetumor is below 10 cm, and any local recurrence should bepalpable on digital rectal examination. None of the recur-rences in this series were recurrent villous adenomas or

incidental carcinomas arising within a recurrent villous ad-enoma. Only 30% of those evaluable were node positive. Ina series from Massachusetts General Hospital, 17 of 18 localrecurrences were mucosal (21).

LVI was the only significant predictor for local recur-rence in both univariate and multivariate analysis in thisstudy. LVI was also noted to be significant by Willettet al.(24). In one series, the risk of local recurrence was relatedto lymphatic rather than vascular invasion (34). In mostseries, the presence of LVI was not recorded or the numberof patients was too small to allow evaluation of the prog-nostic significance of LVI (17–20, 35, 36).

Margin status was not found to be a significant predictorof local recurrence. Bouvetet al. (22) reported an increasedrisk of local recurrence if margins were positive in bothunivariate and multivariate analysis. Others have not re-ported an increased risk of local recurrence with positivemargins (17, 20). A number of series required negativemargins as entry criteria (18, 24, 35). Reporting of marginsis problematic if the specimen is fragmented, because thepathologist is unable to determine the true margin of thetumor. In the present series, any specimen received in morethan one piece was considered to be a fragmented specimen.Fragmentation of the specimen was a significant predictorof OS, DFS, and LRFR in univariate analysis, but not inmultivariate analysis.

Where local recurrence rate was reported actuarially by Tcategory, the local recurrence rate for T1 lesions was 5%(22), for T2 lesions was 20–31% (20, 22), and for T3lesions was 27% (22). T category was not found to influencelocal recurrence in other series (16–18). In our series, the5-year local relapse rates were 39%, 21%, and 25% for T1,T2, and T3 lesions, respectively.

T1 patients in this series had a particularly poor localcontrol rate (61%) compared to those found in other series(19, 22). This difference might be related to patient selec-tion. T1 lesions with good prognostic features are not nor-mally offered adjuvant radiotherapy after adequate localexcision. Patients with T2 or T3 lesions, regardless ofhistopathologic or other features, routinely receive adjuvantradiotherapy if they are not candidates for surgery. Indeed,higher stage lesions with poor prognostic features are likelyto be treated with radical surgery and adjuvant chemoradio-therapy, whereas local excision and radiotherapy is reservedonly for those with good pathologic features. There was aslight increased incidence of fragmentation (T1 29%, T225%), lymphovascular invasion (T1 41%, T2 29%), andpositive margins (T1 42%, T2 36%) in T1 lesions comparedto T2 lesions. This difference, however, does not appear tobe sufficient to completely explain the poor results in T1lesions. There was also no evidence that T1 lesions werebulkier tumors compared to T2 lesions. The median sizes ofT1, T2, and T3 lesions in this series were 2.3, 3.1, and 4 cm,respectively. Overall tumor size furthermore did not appearas a significant factor in this series. Some investigators havefound size to be significant (22) or to approach significance


(16), and many investigators restrict local excision to le-sions less than or equal to 4 (19, 34, 35) or 5 cm (18).

Similar to the present results, most series failed to estab-lish the significance of tumor grade, because the vast ma-jority of patients have well- and moderately differentiatedlesions (17, 18, 22). In the series by Willettet al., (24) localcontrol rate was significantly worse for poorly differentiatedcompared to well- and moderately differentiated cancers.

The main criticism concerning local therapy for rectalcancer centers on the adequacy of excision of the primaryand staging of regional lymph nodes. Radical surgical serieshave reported node-positive rates for Stage T1 tumors of0–21%, for Stage T2 of 12–28% (37), and for T3 of 36–68% (38–41). When sensitive immunohistochemical tech-niques were used, micrometastases have been observed inup to 50% of lymph nodes that were negative by conven-tional pathologic standards (42). The significance of thisfinding is uncertain and has not been correlated with re-duced survival.

The majority of patients in this report received a dose of50 Gy in 20 fractions (85%). Published doses have rangedfrom 44.6 to 67 Gy (16–18, 20–24, 34–36). Where doseresponse has been analyzed, there is no evidence for a doseresponse over 44 Gy (8, 16). The majority of the patientsreported here (85%) were treated in a single phase to avolume including the primary and perirectal nodes only. Noeffort was made to treat the true pelvis in its entirety. Mostother series include the true pelvis in at least the first phase(16–18, 20–22, 24, 34). All of our local recurrences were at

the site of the primary. Our control rates are similar to thosein studies using large volumes, and these results suggest thatit may not be necessary to treat the whole pelvis.

Chemotherapy was not given to patients as part of theirprimary treatment. In many series, chemotherapy was givenconcurrently with radiotherapy to all patients (19, 23, 34,35), or to selected patients (16, 17, 19, 20–22, 24). Adjuvantchemotherapy has been demonstrated to improve local con-trol and survival in node-positive rectal cancer (29, 30) andhas become the standard for the adjuvant treatment of T3 ornode-positive rectal cancer (43). It seems reasonable toextrapolate this to the setting of local excision, particularlywhen the risk of positive nodes is significant. However, theincidence and severity of acute toxicity appeared higher inseries where chemotherapy was given concurrently withradiotherapy (19, 35).

In this study, the univariate analysis demonstrates that therecurrence rate is significantly higher for all patients withLVI or with fragmented specimens. The presence of LVIremained significant in the multivariate analysis. We nowrecommend radical surgery for all patients with LVI orfragmented specimens. However, for patients in this high-risk group who refuse radical surgery or are medically unfitfor a radical surgery, transrectal excision and postoperativeRT provide local control in over 50% of patients, and it ispossible that this rate may be improved by adding concur-rent chemotherapy. For patients with no LVI, local excisionand postoperative RT appears to be an effective alternativeto abdominoperineal resection.

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Local excision and postoperative radiotherapy for distal rectal cancer